Some pharmaceutical compositions as for example injectable compositions require to be sterilised prior to administration. These pharmaceutical compositions have to be manufactured and stored under sterile conditions. A multi-layered plastic polymeric container for the storage of a chemical composition that may or may not be sterilised is disclosed in WO2008/152122. The herein disclosed bottles have a volume of 50 ml to 500 ml. A plastic container made of polyethylene naphthylate with a closure device for storing and preserving a composition of sodium benzoate and cefdinir is disclosed in WO2007/087214.
It is crucial that the material of the container is pharmaceutically acceptable meaning that it should not interfere with the pharmaceutical composition or alter the quality of the compositions. The reverse must also be valid, that the pharmaceutical compositions should not interfere or alter the nature and/or composition of the container. Any alterations that may occur can result in the migration of chemicals from and to the container material and/or the pharmaceutical composition. Any chemicals from the container material that may mix with the solution will be impurities within the solution that may affect the solution by degrading the composition or may not be tolerated in any other way. Degradation may also occur over time under the action of oxygen, light and/or temperature. If the container and/or solution has been sterilised by for example irradiation, then this may also result in degradation of any of the material. The chemical properties of the pharmaceutical composition, such as the stability of the active ingredient may alter over time because of any interactions and thus reduce the lifetime of the formulation. Another interaction that has to be avoided is adsorption of any of the components, especially sodium benzoate, within the solution to the material of the bottle.
The pharmaceutical composition comprising meloxicam is a very frequently used drug for veterinary medicine for the treatment of for example pain, post-operative pain, inflammation, fever, diarrhea, lameness, problems with the locomotor apparatus, respiratory complaints, osteoarthritis. It is available not only in different formulations but also in dosage forms which are optimised for the use of a pharmaceutical composition for several animal species.
Oral suspensions of meloxicam with a concentration of 1.5 mg/ml are established for the treatment of dogs for more than 10 years. This formulation is revealed in the patent application WO99/49845.
In addition it was found that the drug is suitable for the treatment of cats as well. The palatability of the formulation in both dogs and cats is exceptional, thus ensuring an excellent compliance of drug treatment. For cats an oral suspension with 0.5 mg/ml of meloxicam has been developed, which allows accurate dosing according to the body weight of the animal.
Oral suspension of 0.5 mg/ml meloxicam for chronic treatment has been approved. This suspension is available in 25 ml high-density polyethylene (HDPE) bottles filled with 15 ml of the suspension. For both the 1.5 mg/ml and the 0.5 mg/ml suspension a decrease of the sodium benzoate content over time can be observed. It could be proven that this loss of the preservative is explained not by chemical degradation, but by adsorption of sodium benzoate to the bottle wall. Sodium benzoate is used as the preservative and is the only substance of the solution, which can be active as a preservative and because of its adsorption it needed to be assessed whether the formulation is still adequately preserved over the shelf-life of the product. It could be demonstrated that at a sodium benzoate content of 70% of the label claim of 0.15 mg/ml the formulation is still fulfilling all requirements of the European Pharmacopoeia for preservative efficacy. This approach of increasing the preservative in order to prolong the potential shelf-life of the formulation is undesirable as it cannot be completely excluded that preservatives may cause irritation or allergic reactions. It would be an unnecessary amount of preservatives that would be given to the animals.
For the acute treatment in cats a smaller bottle is required which contains enough of the pharmaceutical solution for the treatment of up to five (5) days. A container with approximately three (3) ml of an oral suspension comprising 0.5 mg/ml meloxicam would fulfil these requirements. In addition such a composition would allow the treatment of several other species like small dogs (with a body weight of 0.5 kg up to 5 kg), rabbits and guinea pigs. Thus the problem underlying the present invention was to provide a plastic container containing a pharmaceutical composition comprising benzoic acid or a derivative thereof or a pharmaceutical acceptable salt thereof and a COX-inhibitor of the oxicam-type or a pharmaceutical acceptable salt thereof avoiding a significant loss of benzoic acid or a derivative thereof during storage. Furthermore, the problem underlying the present invention was to provide a plastic container containing a pharmaceutical composition comprising sodium benzoate and meloxicam avoiding a significant loss of sodium benzoate during storage.